Conservation of receptor antagonist anti-tumor activity by epidermal growth factor receptor antibody expressed in transgenic corn seed

Recombinant protein production in plants such as corn is a promising means to generate high product yields at low comparable production cost. The anti-EGFR monoclonal antibody C225, cetuximab, is a well-characterized receptor antagonist antibody recently approved for the treatment of refractory colorectal cancer. We initiated a study to test and compare the functional activity of glycosylated and aglycosylated C225 produced in stable transgenic corn seed. Both corn antibodies were shown to be functionally indistinguishable from mammalian-derived C225 in demonstrating high-affinity binding to the EGF receptor, blocking of ligand-dependent signaling, and inhibiting cell proliferation. In addition, consistent with cetuximab, both corn antibodies possessed strong anti-tumor activity in vivo. Acute dose primate pharmacokinetic studies, however, revealed a marked increase in clearance for the glycosylated corn antibody, while the aglycosylated antibody possessed in vivo kinetics similar to cetuximab. This experimentation established that corn-derived receptor blocking monoclonal antibodies possess comparable efficacy to mammalian cell culture-derived antibody, and offer a cost effective alternative to large-scale mammalian cell culture production.     

Is the CAG repeat of mitochondrial DNA polymerase gamma (POLG) associated with male infertility? A multi-centre French study

BACKGROUND: Recent data emphasized the implication of polymerase gamma (POLG) CAG repeats in infertility, making it a very attractive gene for study. A comparison of POLG CAG repeats in infertile and fertile men showed a clear association between the absence of the usual 10-CAG allele and male infertility, excluding azoospermia. It has also been suggested that the POLG gene polymorphism should be considered as a possible contributing factor in unexplained couple infertility where semen parameters are normal. In this study, we investigated the POLG CAG repeats, in a well-defined population of patients with severe male factor infertility. METHODS: We conducted a large study of POLG CAG repeats in 433 infertile and 91 fertile, normozoospermic and healthy males. In all subjects, phenotypic data, including semen parameters, hormonal status and clinical profiles, were available. RESULTS: Thirteen 'homozygous mutants' (3%) were found among the 433 idiopathic infertile patients. The follow-up of the 13 'homozygous mutant' resulted in pregnancy for more than half of the couples, through assisted reproductive techniques or even spontaneously. In addition, one 'homozygous mutant' was identified in 91 fertile men (1.1%) CONCLUSION: Under our conditions, our study does not confirm any relationship between the polymorphic CAG repeat in the POLG gene and male infertility.     

Rapid detection of gastric Campylobacter pylori colonization by a simple biochemical test.

A simple and rapid urease test to detect Campylobacter pylori infection was evaluated with bacterial culture as the "gold standard." The test was compared with the Gram stain and the conventional Christensen urease test. The culture method detected C. pylori in 29 of 49 gastric biopsy specimens. The rapid urease test showed 27 positive samples within 1 h at 55 degrees C (specificity, 100%; sensitivity, 93%) and 18 at room temperature (specificity, 100%; sensitivity, 62%). The Gram stain exhibited a sensitivity of 86% and a specificity of 91%. The conventional Christensen urease test detected C. pylori in only 4, 10, and 18 samples after 24, 48, and 72 h, respectively (sensitivities, 12, 36, and 60%, respectively; specificities, 95, 95, and 83%, respectively). We conclude that the rapid urease test is simple and highly specific for the detection of C. pylori and that it can be performed with small amounts of sample.     

The caudal regression syndrome in infants of diabetic mothers

Ultrasonography as part of the pre-natal diagnosis in high risk pregnancies may detect a number of fetal malformations that need to be re-evaluated for continuation or termination of pregnancy. Two fetuses, in two different patients with diabetes mellitus, were found to have significant intrauterine malformations detected by ultrasonography at 18 and 20 weeks gestational age, respectively. Post-mortem examination on both fetuses demonstrated the findings known as the caudal regression syndrome. The clinico-pathological features and obstetrical management of diabetic mothers whose pregnancies are complicated with this rare malformation are discussed.     

An outbreak of Plasmodium vivax malaria among heroin users in Spain

We report the first outbreak of induced malaria among heroin users in Spain, and the first one caused by Plasmodium vivax in Europe. Five drug addicts from Madrid, who had never travelled to endemic areas, were admitted to hospital with fever and splenomegaly. Four had P. vivax malaria with low parasitaemia, ranging from 1 to 3% red blood cells. The fifth case was considered a "seropositive contact" because he had fever and positive malaria indirect fluorescent antibody test but negative blood smear. The source of infection was a young drug addict, who had often travelled to Equatorial Guinea. Another heroin user with a diagnosis of malaria refused to be admitted to our hospital for further study. All had shared contaminated injection equipment. Treatment with chloroquine was effective and none had recrudescence of malaria during a mean follow-up of six months. Drug addicts with unexplained fever may have been infected by malaria transmitted by sharing injections.     

Detection of p53 mutations in gynecologic tumors by means of a simple, nonradioactive minigel method of PCR-SSCP analysis

We studied 22 gynecological tumors for mutations in exons 5 through 8 of the p53 gene by means of SSCP analysis, using a simplified, nonradioactive technique developed at our laboratory. In order to test the procedure, we carried it out in parallel with the usual radioactive one. Two coincident mutations (in exons 5 and 8) were found by means of both methods. However, an additional one in exon 6 was found by means of our nonradioactive technique. This simplified method for SSCP-analysis of the p53 gene in human tumors is faster, easier and cheaper to perform than the conventional radioactive method, and yields equivalent results. It could be thus an excellent candidate for routine use in the clinical setting.     

Quantification of children's hand and mouthing activities through a videotaping methodology.

A videotaping methodology has been developed for use in quantifying the types and frequencies of children's hand and mouthing activities that could lead to exposure to environmental pollutants via dermal and ingestion pathways. Twenty children in day care, ages 3-6 years and 10 children in residences, ages 2-5 years, were videotaped during their waking hours for 1 day. Parents of each child completed questionnaires for the purpose of evaluating the accuracy of parental reports of hand-to-mouth rates. Videotapes were translated as quantifiable activities by two trained observers whose reporting reliability was checked throughout the investigation. Results determined that reliability of the videotaping method was very good, even over a year post-training. From videotape data, the average hand-to-mouth frequency rate was determined to be 9.5 contacts/h. These values are considerably higher than the current default value of 1.56 contacts/h under consideration by the EPA.